Dimethyldisulfide reduced the effective concentration of selenocystamine for cytotoxicity to L1210 murine leukemia cells in culture by two orders of magnitude. It also elicited a marked increase in the toxicity of selenocystine. The results are interpreted as due to an improved uptake of the selenium compounds via the mixed selenosulfides. This is supported by the observation that the toxicity of selenocystine promoted by dimethyldisulfide was reduced in the presence of a high concentration of leucine. This indicates that the selenosulfide adduct, 4-selenamethionine, was taken up by the cell via the leucine-preferring transport system. The specificity of the disulfide for promotion of selenocystine toxicity is more rigorous than that for promotion of growth under conditions of limiting cystine availability. Under the latter conditions, the oxidized form of mercaptoethanol, hydroxyethyldisulfide, was highly effective, but under the former it was a poor potentiator of toxicity. At present we do not know whether this difference is due to the rate of thiol-selenide interaction or to uptake by the cell of the selenosulfide compound. Cells inhibited in growth by the selenosulfide adducts were still viable when washed free of the inhibitor after incubation for 8 hours. The mechanism of inhibition and possible differences in specificity of the disulfide among various cell types will be investigated. The goal of this project is to provide a fundamental understanding of factors promoting selenide uptake and to apply this information for use of diselenides in cancer chemotherapy.